The mechanism(s) of resistance to treponemal infection has not been elucidated. We have shown that serum or T-cells obtained from inbred hamsters immune to Treponema pallidum Bosnia A or T. pertenue can confer protection on hamsters to challenge with the homologous strain. The objectives of the present proposal are to determine: (1) whether macrophages specifically (T cells) or nonspecifically activated can kill treponemes in the presence or absence of treponemal immune serum; (2) whether immune treponemal T-cells or their products can kill treponemes; (3) whether specific resistance to infection with T. pallidum or T. pertenue can be detected with whole or fractionated (IgM, IgG2 or IgG1) immune serum; (4) whether specific resistance can be conferred on recipients with B cells; (5) in vitro responses of syphilitic and frambesial T-cells to mitogens and treponemal antigens; (6) whether treponemal lymphocytes (T or B cells) or macrophages can impair the mitogenic responses of normal hamster lymphocytes; (7) the temporal relationship between the development and regression of treponemal lesions and infiltration of macrophages and T and B cells into these tissues. The cellular infiltration of the inguinal lymph nodes will also be examined since they teem with treponemes; and (8) whether T cells or immune serum from hamsters immune to T. pallidum Bosnia A, T. pallidum Nichols or T. pertenue can confer protection on recipients to challenge with the heterologous strain. Investigation of the mechanism of resistance by which hamsters respond to treponemal infection may delineate the mechanism by which humans respond to syphilitic or frambesial infection.